POST-POLIO SYNDROME
NIH GUIDE, Volume 21, Number 5, February 7, 1992
PA NUMBER: PA-92-40
P.T. 34
Keywords:
Infectious Diseases/Agents
Epidemiology
Pathophysiology
Immunology
Disease Model
National Institute of Neurological Disorders and Stroke
PURPOSE
The National Institute of Neurological Disorders and Stroke (NINDS)
encourages the submission of applications for research grants related
to the post-polio syndrome. The NINDS invites grant applications to
support research in all aspects of the post-polio syndrome including
epidemiology, diagnosis, pathophysiology, immunology, therapy, and the
development of animal models.
HEALTHY PEOPLE 2000
The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention goals of "Healthy People 2000," a
PHS-led national activity for setting priorities. This program
announcement, Post-polio Syndrome, is related to the priority area of
diabetes and chronic disabling conditions. Potential applicants may
obtain a copy of "Healthy People 2000" (Full Report: No.
017-001-00474-0, or Summary Report: Stock No. 017-001-00473-1) through
the Superintendent of Documents, Government Printing Office,
Washington, DC 20402-9325 (Telephone: 202-783-3238).
ELIGIBILITY REQUIREMENTS
Applications may be submitted by foreign and domestic, for-profit and
non-profit organizations, public and private, such as universities,
colleges, hospitals, laboratories, units of State or local governments,
and eligible agencies of the Federal government. Applications from
minority individuals and women are encouraged.
MECHANISMS OF SUPPORT
Support for this program announcement will be the Research Project
Grant (R01), Research Program Project (P01), Research Center Grant
(P50), and First Independent Research Support and Transition (FIRST)
Award (R29). Prospective applicants are encouraged to communicate with
the NINDS staff contact listed under INQUIRIES regarding the
appropriate funding mechanism. Both basic science and clinical
investigations are encouraged to address relevant research issues.
RESEARCH OBJECTIVES
Background
Survivors of paralytic poliomyelitis have begun to suffer renewed
neurological and neuromuscular symptoms decades after maximum recovery
from the acute disease. Symptoms include a form of progressive
muscular atrophy that involves new muscle weakness affecting certain
muscle groups, pain, fatigue, and decreased physical endurance.
Individuals who have fully recovered from the initial episode and those
who still have residual effects are at risk. A number of terms have
been proposed to describe these late effects including post-polio
syndrome, post-polio motor neuron disease, and post-polio muscular
atrophy.
Estimates of the number of survivors of paralytic poliomyelitis in the
United States vary widely, from about 250,000 to over 1 million. A
1984 epidemiological study performed by the Mayo clinic found that 25
percent of survivors had renewed symptoms, but a later follow-up of a
sample of the original respondents showed that 66 percent were
experiencing new weakness.
Pathologic mechanisms involved in the post-polio syndrome are not
understood, and there is evidence supporting several etiological
theories. Changes in the motor neuron have been studied extensively.
After recovery from acute polio, axons of surviving motor neurons
sprout to reinnervate muscles whose original motor neuron did not
survive. It is hypothesized that this process is ongoing for several
years, after which the capacity of the motor neuron to reinnervate
additional muscles is reached and the nerve terminals begin to
degenerate.
A recent report of IgM antibodies to the polio virus in some patients
with recurring weakness suggests that late effects of the long dormant
polio virus may play a role. Other hypotheses that have been studied
include neuromuscular changes caused by premature aging in polio
patients, an immunological mechanism, and spinal cord changes affecting
motor neurons.
Research Goals and Scope
Multidisciplinary or collaborative studies of the post-polio syndrome
are encouraged. Examples are given below, but applications are not
limited to these areas of research:
o Epidemiological studies to determine the prevalence of post-polio
syndrome and to develop standardized diagnostic criteria.
o Pathogenetic studies emphasizing the relative stability of
reinnervation following infection with the polio virus, terminal
sprouting, and growth factors.
o Animal models to study the pathogenesis of the original insult,
reinnervation, possible reappearance of symptoms, and restoration of
function.
o Use of new molecular biological techniques such as cloned polio
cDNAs and the polymerase chain reaction (PCR) to detect the polio
virus.
o Development of strategies of immunotherapy if it is determined that
an autoimmune mechanism is involved.
o Development of therapeutic strategies to improve or restore
neuromuscular function.
STUDY POPULATIONS
SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH
POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL
RESEARCH STUDY POPULATIONS
NIH and ADAMHA policy is that applicants for NIH/ADAMHA clinical
research grants and cooperative agreements will be required to include
minorities and women in study populations so that research findings can
be of benefit to all persons at risk of the disease, disorder or
condition under study; special emphasis must be placed on the need for
inclusion of minorities and women in studies of diseases, disorders and
conditions which disproportionately affect them. This policy is
intended to apply to males and females of all ages. If women or
minorities are excluded or inadequately represented in clinical
research, particularly in proposed population-based studies, a clear
compelling rationale must be provided.
The composition of the proposed study population must be described in
terms of gender and racial/ethnic group. In addition, gender and
racial/ethnic issues should be addressed in developing a research
design and sample size appropriate for the scientific objectives of the
study. This information must be included in the form PHS 398 in
Section 2, A-D of the research plan AND summarized in Section 2, E,
Human Subjects. Applicants/offerors are urged to assess carefully the
feasibility of including the broadest possible representation of
minority groups. However, NIH recognizes that it may not be feasible
or appropriate in all research projects to include representation of
the full array of United States racial/ethnic minority populations
(i.e., Native Americans (including American Indians or Alaskan
Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale
for studies on single minority population groups must be provided.
For the purpose of this policy, clinical research is defined as human
biomedical and behavioral studies of etiology, epidemiology, prevention
(and preventive strategies), diagnosis, or treatment of diseases,
disorders or conditions, including but not limited to clinical trials.
The usual NIH policies concerning research on human subjects also
apply. Basic research or clinical studies in which human tissues
cannot be identified or linked to individuals are excluded. However,
every effort should be made to include human tissues from women and
racial/ethnic minorities when it is important to apply the results of
the study broadly, and this should be addressed by applicants.
For foreign awards, the policy on inclusion of women applies fully;
since the definition of minority differs in other countries, the
applicant must discuss the relevance of research involving foreign
population groups to the United States' populations, including
minorities.
If the required information is not contained within the application,
the review will be deferred until the information is provided.
Peer reviewers will address specifically whether the research plan in
the application conforms to these policies. If the representation of
women or minorities in a study design is inadequate to answer the
scientific question(s) addressed and the justification for the selected
study population is inadequate, it will be considered a scientific
weakness or deficiency in the study design and will be reflected in
assigning the priority score to the application.
All applications for clinical research submitted to NIH are required to
address these policies. NIH funding components will not award grants
or cooperative agreements that do not comply with these policies.
APPLICATION PROCEDURES
Applications must be submitted on the grant application form PHS 398
according to instructions contained in the application kit.
Applications submitted after May 1, 1992, are to use the 9/91 revision
of the form PHS 398. Application kits are available from most
institutional business offices and may be obtained from the Office of
Grants Inquiries, Division of Research Grants, Westwood Building, Room
449, National Institutes of Health, Bethesda, MD 20892, telephone
301-496-7441.
Check "yes" in item two on the face page of the application and type
"Post-Polio Syndrome, PA-92-40."
Applicants for the P01 or P50 must use the application format as
described in the NINDS pamphlet, "Application Guidelines: Program
Project and Clinical Research Center Grants," that may be obtained from
the contacts listed under INQUIRIES.
Deadlines for the receipt of applications are February 1, June 1, and
October 1. The completed original application and six legible copies
must be sent or delivered to:
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD 20892
REVIEW PROCEDURES
Applications will be assigned on the basis of established Public Health
Service referral guidelines. Applications will be judged on scientific
merit and program relevance in accordance with NIH policy and
procedures involving peer review. An initial review will be made by an
appropriate study section of the Division of Research Grants for
research grants and FIRST awards and by an appropriate institute
committee for program projects and centers. A second level of review
will be made by an appropriate national advisory council.
AWARD CRITERIA
Applications will compete for available funds with all other approved
applications. The following will be used in making funding decisions:
o Quality of the proposed project as determined by peer review
o Availability of funds
o Program balance among research areas of the announcement
INQUIRIES
For further information regarding this announcement, potential
applicants may write or call:
Paul L. Nichols, Ph.D.
Developmental Neurology Branch
Division of Developmental, Convulsive, and Neuromuscular Disorders
National Institute of Neurological Disorders and Stroke
Federal Building, Room 8C08
Bethesda, MD 20892
Telephone: (301) 496-5821
For fiscal and administrative inquires regarding this announcement,
potential applicants may write or call:
Dwight H. Mowery, Jr.
Grants Management Specialist
Grants Management Branch
National Institute of Neurological Disorders and Stroke
Federal Building, Room 1004
Bethesda, MD 20892
Telephone: (301) 496-9231
AUTHORITY AND REGULATIONS
This program is described in the Catalog of Federal Domestic Assistance
No. 93.853 Clinical Research Related Neurological Disorders and 93.854
Biological Basis Research in the Neurosciences. Awards are made under
authorization of the Public Health Service Act, Title IV, Part A
(Public Law 78-410, as amended by Public Law 99-150, 42 USC 241 and
285) and administered under PHS grants policies and Federal Regulations
42 CFR 52 and 45 CFR Part 74. This program is not subject to the
intergovernmental review requirements of Executive Order 12372 or
Health Systems Agency review.
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